Lipid-accumulated reactive astrocytes promote disease progression in epilepsy.

Autor: Chen ZP; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China. xiaopengczp@163.com.; Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing, China. xiaopengczp@163.com.; Institute of Artificial Intelligence Biomedicine, Nanjing University, Nanjing, China. xiaopengczp@163.com., Wang S; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China., Zhao X; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China., Fang W; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China., Wang Z; Department of Radiology, the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.; Epilepsy Center, the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China., Ye H; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China., Wang MJ; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China., Ke L; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China., Huang T; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China., Lv P; Department of Radiology, the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China., Jiang X; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.; Institute of Artificial Intelligence Biomedicine, Nanjing University, Nanjing, China., Zhang Q; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.; Institute for Brain Sciences, Nanjing University, Nanjing, China., Li L; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.; Institute for Brain Sciences, Nanjing University, Nanjing, China., Xie ST; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.; Institute for Brain Sciences, Nanjing University, Nanjing, China., Zhu JN; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.; Institute for Brain Sciences, Nanjing University, Nanjing, China., Hang C; Department of Neurosurgery, the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China., Chen D; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China. dijunchen@nju.edu.cn., Liu X; Epilepsy Center, the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. liuxiangyumail@163.com.; Department of Neurosurgery, the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. liuxiangyumail@163.com., Yan C; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China. yanchao@nju.edu.cn.; Chemistry and Biomedicine Innovation Center, Nanjing University, Nanjing, China. yanchao@nju.edu.cn.; Institute of Artificial Intelligence Biomedicine, Nanjing University, Nanjing, China. yanchao@nju.edu.cn.; Epilepsy Center, the Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, China. yanchao@nju.edu.cn.; Institute for Brain Sciences, Nanjing University, Nanjing, China. yanchao@nju.edu.cn.; Engineering Research Center of Protein and Peptide Medicine, Ministry of Education, Nanjing, China. yanchao@nju.edu.cn.
Jazyk: angličtina
Zdroj: Nature neuroscience [Nat Neurosci] 2023 Apr; Vol. 26 (4), pp. 542-554. Date of Electronic Publication: 2023 Mar 20.
DOI: 10.1038/s41593-023-01288-6
Abstrakt: Reactive astrocytes play an important role in neurological diseases, but their molecular and functional phenotypes in epilepsy are unclear. Here, we show that in patients with temporal lobe epilepsy (TLE) and mouse models of epilepsy, excessive lipid accumulation in astrocytes leads to the formation of lipid-accumulated reactive astrocytes (LARAs), a new reactive astrocyte subtype characterized by elevated APOE expression. Genetic knockout of APOE inhibited LARA formation and seizure activities in epileptic mice. Single-nucleus RNA sequencing in TLE patients confirmed the existence of a LARA subpopulation with a distinct molecular signature. Functional studies in epilepsy mouse models and human brain slices showed that LARAs promote neuronal hyperactivity and disease progression. Targeting LARAs by intervention with lipid transport and metabolism could thus provide new therapeutic options for drug-resistant TLE.
(© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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